STAC3D Against the Odds: Characterizing the Musculoskeletal Phenotype of STAC3 Gene Disorder

Area of Science:

• Genetics and Rare Diseases
• Orthopedics
• Clinical Phenotyping

Background:

• STAC3 Disorder (STAC3D) is a rare genetic condition presenting with diverse musculoskeletal abnormalities, myopathic facies, and susceptibility to malignant hyperthermia.
• Initially identified in the Lumbee Native American population, STAC3D is now recognized globally.

Purpose of the Study:

• To comprehensively characterize the musculoskeletal phenotype of STAC3D patients.
• To provide data that aids in the diagnosis and clinical management of STAC3D.

Main Methods:

• Retrospective cohort study of STAC3D patients from 2014-2025 at a single institution.
• Data collection included demographics, genetic testing, musculoskeletal conditions, and surgical management.
• Descriptive and comparative statistics were used to analyze the data.

Main Results:

• The study analyzed 23 STAC3D patients, with a median age of 4 years at data collection.
• High prevalence of musculoskeletal conditions observed: 83% scoliosis, 48% hyperkyphosis, 61% joint contractures, and 61% congenital foot deformities.
• A significant proportion required surgical intervention (57% orthopaedic, 78% non-orthopaedic) and general anesthesia (87%).

Conclusions:

• STAC3D is associated with a wide spectrum of musculoskeletal problems, notably spinal and congenital foot deformities, and joint contractures.
• This study presents the largest North American and second-largest global cohort of STAC3D patients, offering novel insights into its musculoskeletal manifestations.
• The findings aim to improve early diagnosis and inform management strategies for STAC3D patients.